It has recently been recognized that some human retroviruses are capable of replicating in the central nervous system. Their participation in CNS pathology is as yet a matter of speculation. We are studying a murine retrovirus (WM-E) which was originally isolated from wild mice and has the capacity to cause a lower-motor-neuron paralytic disease in some strains of laboratory mice with a 12-20 week latency. The primary goal of this project is to identify the cells in the CNS which replicate this virus and the mechanisms by which this virus cause motor neuron pathology. We have prepared a panel of monoclonal antibodies specific for WM-E in AKR mice which are tolerant to endogenous retrovirus. These antibodies react with the three viral membrane-associated proteins gp70, p15(E) and P15gag and express no cross-reactivity with endogenous viruses of laboratory mice. Using these antibodies to follow virus replication, we have found that neonatal inoculation of both susceptible (NFS) and resistant (AKR, NZB) strains of mice resulted in quantitatively equivalent levels of WM-E virus replication in the spleen and comparable levels of viremia. We have documented that the virus does indeed replicate in the lumbar spinal cord by both immunohistochemistry and infectious center assay of trypsin/collagenase-disrupted tissue. However, no significant difference was found in the levels of virus replication in the lumbar cord of susceptible and resistant strains of mice. In addition, retroviruses which do not cause neurologic disease also replicated in the CNS, but the patterns of replication as detected by EM appear different when compared with that of WM-E. We are currently studying primary cultures of lumbar cord cells in order to identify the specific cell types which are infected by these various viruses. Another retrovirus has now been identified which is unrelated to WM-E, but which also causes paralytic disease in mice. This virus is being molecularly cloned by B. Chesebro and should prove useful in identifying viral genomic sequences responsible for the neuropathology.